5378-94-9Relevant academic research and scientific papers
A novel class of ethacrynic acid derivatives as promising drug-like potent generation of anticancer agents with established mechanism of action
Mignani, Serge,El Brahmi, Nabil,El Kazzouli, Sa?d,Eloy, Laure,Courilleau, Delphine,Caron, Joachim,Bousmina, Mosto M.,Caminade, Anne-Marie,Cresteil, Thierry,Majoral, Jean-Pierre
, p. 656 - 673 (2016)
The well-known diuretic Ethacrynic acid (EA, Edecrin), showing low anti-proliferative activities, was chemically modified at different positions. The new EA derivatives have been tested in?vitro in anti-proliferative assays on both tumor KB (epidermal carcinoma) and leukemia HL60 (promyelocytic) cells suitable targets for anticancer activity. Reduction of the α-β double bond of EA completely abolished anti-cancer activities, whereas introduction of either 2-(4-substituted phenyl)ethanamine (series A) or 4-(4-substituted phenyl)piperazine (series B) moieties generated compounds showing moderate to strong anti-proliferative activities against human cancer cell lines. Several substitutions on the phenyl of these two moieties are tolerated. The mechanism of action of the EA derivatives prepared in this study is more complex than the inhibition of glutathione S-transferase π ascribed as unique effect to EA and might help to overcome tumor resistances.
Discovery of a Covalent Kinase Inhibitor from a DNA-Encoded Small-Molecule Library × Protein Library Selection
Chan, Alix I.,McGregor, Lynn M.,Jain, Tara,Liu, David R.
, p. 10192 - 10195 (2017)
We previously reported interaction determination using unpurified proteins (IDUP), a method to selectively amplify DNA sequences encoding ligand:target pairs from a mixture of DNA-linked small molecules and unpurified protein targets in cell lysates. In this study, we applied IDUP to libraries of DNA-encoded bioactive compounds and DNA-tagged human kinases to identify ligand:protein binding partners out of 32 096 possible combinations in a single solution-phase library × library experiment. The results recapitulated known small molecule:protein interactions and also revealed that ethacrynic acid is a novel ligand and inhibitor of MAP2K6 kinase. Ethacrynic acid inhibits MAP2K6 in part through alkylation of a nonconserved cysteine residue. This work validates the ability of IDUP to discover ligands for proteins of biomedical relevance.
Amide derivatives of ethacrynic acid: Synthesis and evaluation as antagonists of Wnt/β-catenin signaling and CLL cell survival
Jin, Guangyi,Lu, Desheng,Yao, Shiyin,Wu, Christina C.N.,Liu, Jerry X.,Carson, Dennis A.,Cottam, Howard B.
body text, p. 606 - 609 (2009/09/06)
A series of amides of ethacrynic acid was prepared and evaluated for their ability to inhibit Wnt signaling and decrease the survival of CLL cells. Several of the most potent derivatives were active in the low micromolar range. Reduction of the α,β-unsatu
Highly chemoselective hydrogenation method using novel finely dispersed palladium catalyst on silk-fibroin: Its preparation and activity
Ikawa, Takashi,Sajiki, Hironao,Hirota, Kosaku
, p. 2217 - 2231 (2007/10/03)
A palladium-fibroin complex (Pd/Fib) was prepared by soaking silk-fibroin in MeOH solution of Pd(OAc)2 for 2 days (under Ar atmosphere) - 4 days (under air). Pd(OAc)2 was gradually absorbed by fibroin and the rapid reduction of fibroin conjugated Pd(OAc)2 proceeded with MeOH as a reductant at room temperature to be the Pd(0) complex. Pd/Fib catalyzed chemoselective hydrogenation of acetylenes, olefins and azides in the presence of aromatic ketones and aldehydes, halides, N-Cbz protective groups and benzyl esters which are readily hydrogenated using Pd/C or Pd/C(en) as a catalyst.
